A group of government visitors arrive at the Military installation Mount Weather, disembarking from a helicopter to be escorted via bus into the facility. One of the men is Fox Mulder, in a suit, who sneaks away from the group and into one of the base's intelligence stations. After using a keycode to enter a computer room, Mulder accessed a tactical file and reads the screen, which displays the phrase "End Game" and the date December 22, 2012. Before he can continue, he becomes aware of somebody approaching and hides. The man who enters is Knowle Rohrer, who instantly notices that the computer has been accessed. Mulder jumps out of the shadows and attacks Rohrer, but is easily overpowered. He flees, with Rohrer following.

As he sprints down a tunnel towards an escape route, Mulder notices a man standing in the doorway watching him. After hesitating, he rushes through and the man seals the door behind him, locking out Rohrer. Mulder turns to see that the man is in fact Alex Krycek. Although Mulder angrily questions how this is possible, Krycek calmly tells him to leave, and that "there's others". The apparition of Krycek disappears, and Mulder runs down a walkway over a laboratory, but is confronted again by Rohrer, who has outflanked him. As Mulder attempts to escape via a ladder, he is grabbed by Rohrer, who tries to kill Mulder with his bare hands. Noticing electrical pylons below the walkway, Mulder forces Rohrer over the gantry and survives by holding perilously to the handrail. Rohrer, meanwhile, falls into the pylons and is violently electrocuted. As Mulder climbs back onto the walkway, he is confronted by armed guards and arrested.

Mulder is thrown into a stockade by the military. During his time in his cell, he is frequently visited by a guard who demands to know what he is thinking. After being beaten for his initial sarcasm and told "wrong answer", he is visited again, and the question is repeated with Mulder this time admitting that he is thinking about his son, and his son's mother. He is again punished. Eventually, when the guard enters and asks the question again, Mulder says that he "has failed" and that he deserves the most severe punishment for his crimes. Believing that he has been successfully indoctrinated, the guards desist.

At home, Scully receives a phone call from Skinner, telling her that Mulder has been arrested by the military at Mount Weather for the murder of a military man.

The two immediately go to visit him, and are shocked when they see him apparently talking to himself in his cell. Scully greets him emotionally, but she is stung by Mulder's blank response, as is Skinner. Mulder says that he deserves to be where he is and that he is a guilty man. When the pair are forced to leave, Mulder turns back to the corner of his cell and asks "Why are you helping me?" At this point, the apparition of Krycek reappears and replies "Because you can't do this alone". When Mulder is taken away by the guards, the apparition once again disappears.

Scully informs Doggett and Reyes about Mulder's incarceration and both are stunned. The news that the alleged victim is Knowle Rohrer is greeted by scorn, with both testifying to the impossibility of this. Skinner states that there are thirty witnesses that say Mulder pushed Rohrer to his death and that Mount Weather is allegedly the base of a shadow government.

Kersh speaks with General Suveg at Quantico and is told that as a compromise between the Marine Corps and the FBI the trial arranged for Mulder will be overseen by an FBI panel under the laws of Military Court. Kersh says he is uncomfortable with the situation especially after Suveg makes it clear that he wants a guilty verdict and that Mulder will not be provided with a lawyer. Despite his unease, Kersh accepts.

Scully visits Mulder for a second time along with Skinner this time in an empty room. After scaring the pair by way of a practical joke, Mulder laughs and reveals that he is in fact fully in control of himself. He passionately kisses Scully admitting to how much he has missed her, and tells her that his initial coldness was a necessary ruse when in front of the guards. Mulder claims that the trial he faces is rigged and that the truth is what is really on trial. Skinner cites the witness testimony as the strongest evidence against Mulder. Mulder asks Skinner to act as his lawyer much to Skinner's surprise. Doggett and Reyes arrive, and after a brief greeting, Doggett informs them that the government has recovered Knowle Rohrer's body. The news is received with shock.

Some time later, Scully visits Mulder alone. She confesses that she is terrified of what will happen to Mulder and that she doesn't want to lose him yet again. She also admits tearfully to giving William up for adoption, although Mulder confirms that Skinner already told him. He comforts Scully, telling her that he missed both her and William greatly. Scully asks Mulder where he has been, and Mulder replies New Mexico, where he was "looking for the truth", but he says he can not tell her what it was he found there.

The following morning, Skinner arrives at the appointed courtroom and is greeted by Special AgentKallenbrunner, who will be the main lawyer for prosecution due to his experience as a prosecutor. The panel enters and includes Kersh and Toothpick Man. They begin proceedings by calling in Mulder and ask Skinner to call his first witness. Skinner states his disapproval for the trial, and asks that it be thrown out, citing that "this is not a court of law". Kersh rejects this plea, and also denies the right to delay, as Skinner's first witness, Marita Covarrubias, can not be found in order to testify. They move that he call his next witness. When Skinner states that he wants his protest noted in the minutes, he is horrified to hear that the panel is acting as sovereign and that there is no record. Mulder insists that Skinner continue. Skinner calls Scully as the first witness, and she gives testimony that through her work with Mulder she has learned that a conspiracy to hide the existence of extraterrestrials, and that she believes life was begun by alien matter on a meteor that crashed on earth thousands of years prior. She goes on to state that a virus, the black oil, infected early man and changed his physiology. She states that information on the alien race was found in the databanks of the crashed UFO at Roswell, and captured it's crew for scientific research. The intelligence stated that colonization of the Earth would begin on 22 December 2012. She goes on to claim that her abduction was part of an Alien supported Government operation to create an alien-human hybrid. Skinner finishes his questioning, and hands over to Kallenbrunner, who makes clear his disbelief of Scully's claims and asks for some proof. When Scully doesn't respond to this, Kallenbrunner states that she and Mulder were lovers and that she had his child. Skinner angrily objects, and Kallenbrunner immediately dismisses her.

As the next witnesses, Skinner calls Jeffrey Spender, who's ravaged appearance shocks Kallenbrunner and shames the panel. After sitting down, Mulder looks at him in astonishment, before nodding slightly in respect, a gesture returned by Spender. With Skinner questioning, Spender states that his father shot him in the face after learning of his place at the top of the conspiracy. He admits that he is Mulder's half-brother, after Cigarette-Smoking Man had an affair with Teena Mulder. Spender states that as part of the syndicate's deal with the colonists, each member was forced to give up a loved one, and that after being taken initially, Mulder's sister lived with CSM and him before dying in 1987 after horrendous tests. He goes on to say that after he survived being shot, he was subjected to the same tests. When a sympathetic Kallenbrunner says that Spender's father should be brought to justice, Spender states that he believes his father his dead. Kallenbrunner goes on to cite reports made by Spender about Mulder's arrogance and aggression at the FBI as discrediting him. Spender attempts to dismiss these reports, but is unable to do so before he himself is dismissed.

In New Mexico, a young man speeds through the desert on a motorbike to a small secluded caravan. He arrives and walks inside, where Gibson Praise is living. Gibson states that Mulder needs his help, and starts making preparations to leave immediately.

Mulder is visited in his cell once more by Scully, who pleads with him to cut a deal in which he would plead guilty to a lesser charge. Mulder states that he would rather die then give in to them, horrifying Scully. He says that everything he has ever worked on depends on him sticking to the truth, but he still refuses to admit what he saw. Scully emotionally tells him that she is fighting for the two of them, before walking out. After she is gone, Mulder is startled by a familiar voice and demands to know who is there. X steps out of the shadows, and asks what Mulder is doing. Mulder defiantly states that he will reveal the truth, which X scorns, stating that the men he is dealing with will not hear it, and that he must do more. X hands Mulder a piece of paper, written on it is Marita Covarrubias's address. When he looks up, X is gone.

At his apartment, Doggett is attempting to get access to Rohrer's body, and is on the phone to an army receptionist who hangs up on him. Reyes worriedly tells him that there is someone in the yard, and Doggett sees someone running round the house. He confronts the person at gunpoint, and it proves to be Gibson's friend. When Doggett demands an explanation, the boy says that his friend wants to help Mulder but that he can't risk being harmed.

Krycek appears to Mulder at the trial, telling him Marita is in danger

The next morning at the trial, Skinner calls Covarrubias as his witness. Under questioning, she confesses to using her United Nations privileges to help the Syndicate in exchange for money. She speaks of the use of the black oil via bees, and the chase for a vaccine. She goes on to say that she hated the Syndicate, and that upon her betrayal of the group she was punished by being used as a test subject. According to her, the Syndicate had pretended to assist the Colonists while creating their vaccine, and that their efforts were policed by Alien Bounty Hunters. She states that the Syndicate were wiped out by faceless Alien Rebels attempting to prevent colonization. Skinner uses Marita's fear of exposure as evidence that the conspirators are not all dead, and that she can identify them. While Skinner presses her, the apparition of Krycek reappears to Mulder and tells him that if she does identify the men, they will kill her. Mulder immediately tells Skinner to dismiss her. Skinner protests, but relents. Doggett enters and calls over Skinner, informing him that Gibson wants to testify. When Gibson enters, Mulder objects but eventually agrees.

Skinner presents Gibson, and recounts how Mulder and Scully became involved with him during an attempt on his life years earlier. He tells the court of how the "junk DNA" that lies within everyone is active in Gibson, giving him the ability to read minds. When the prosecution mocking asks if he can read everyone's mind, Gibson says yes and he can even read one of the minds of the judges. When asked why that judge was special, Gibson replied "because he's not human." Mulder immediately interrupts Gibson and is hauled out court. Meanwhile, Doggett contacts Scully and tells her that he has acquired Knowle's body after talking with someone who apparently wasn't told to not release the body and had it shipped to Quantico. While Scully performs an autopsy on the corpse, which had been badly burned, she asks Reyes to get ahold of Knowle's medical records. Later, Scully interrupts the court with evidence that the body provided was not Knowle Rohrer's but simply a man who's neck was broken and was set on fire after his death. Kersh angrily tells Scully that she had no authority to examine that body and abruptly adjourns the hearing. Sometime later, Mulder is brought back for sentencing; he has been found guilty of aggravated murder. When addressing the court, Mulder congratulates them for the show they have put on, but that the truth will never stay buried no matter how deep they try to bury it. Back at Scully's home, Doggett answers the phone and after a minute gives everyone the bad news; Mulder has been sentenced to death by lethal injection

Late that night, Mulder is broken out of his cell by Doggett and Skinner; hurrying through the base they run into Kersh, who assists them in helping Mulder escape. The four escape the base despite an alarm being sounded when Knowle Rohrer finds Mulder's cell empty, and meet up with Reyes and Scully. Kersh, when asked what he was doing, responds with "Something I should have done years ago." and tells Scully and Mulder to head north to Canada and take a plane off the continent and that if they aren't gone in 24 hours, they probably won't leave ever. Mulder tells Doggett, Kersh, Reyes and Skinner that they will never be safe now. Doggett responds by saying to "leave that to us." Mulder and Scully take off in an SUV, but a short time later Mulder takes a road heading south. He tells Scully that a man in New Mexico sent him the keycard and codes, and he wants to talk to him. During the trip, Mulder pulls over to relieve himself and is startled by the apparations of the Lone Gunmen who try to convince Mulder to turn around and leave with Scully. He shrugs them off and eventually arrives at the ruins of an Anasazi dwelling seeing smoke coming out of one of the windows, the two investigate and find a woman inside taking care of the Cancer Man. After taunting Mulder and Scully, he tells Scully what Mulder found out; that the alien re-colonization of Earth is set for December 22, 2012 and that he took joy in seeing Mulder finally broken. Back in DC, Doggett and Skinner try to talk to Kersh after finding that Doggett and Reyes's office have been cleaned out and the X-Files have all been removed. The man who Gibson claimed was an alien shuts them out, and Gibson says that he knows where Mulder and Scully are and that they didn't leave as told to. Gibson tells Doggett where they are, and he and Reyes rush there via helicopter to find them. Upon arriving at the ruins, they find Knowle Rohrer pulling up in a van; the two confront him to no effect. As Knowle corners them, he is destroyed by the red magnetite stones that made up the dwellings. Doggett yells to Mulder and Scully to run for it; all four of them drive off as helicopters arrive and blow up the ruins with missiles, killing the Cancer Man.

The episode ends with Scully and Mulder in a motel room in Roswell, New Mexico with Mulder remembering a similar situation during the early years of their partnership. He tells Scully that he didn't tell her of the invasion plans because he didn't want to risk crushing her spirit. The two come to an understanding that, even though much was lost in their search for the truth, their spirits are not broken and that they will never give up fighting regardless of what is laid before them.

At one point in Mulder's cell, he indirectly references the film The Silence of the Lambs when, jokingly, he momentarily assumes the role of Hannibal Lecter and directly refers to Scully as "Clarice", referencing the character of Clarice Starling. Also, the situation in which Mulder and Scully find themselves in, when Mulder makes the reference, echoes several scenes from the earlier film, as Scully's visit to a jailed Mulder mirrors Clarice Starling visiting the imprisoned Hannibal Lecter.

This episode was originally to end with a scene featuring the "Toothpick Man" and PresidentGeorge W. Bush, with an impersonator playing the role of the president. However, the scene was later deleted.

The final scene of the episode is a bookend to a scene in the pilot episode, in which the audience first learns about the abduction of Mulder's sister, and uses the same establishing shot of a hotel that was first seen in the pilot.

As hinted at by the Cigarette Smoking Man, December 22, 2012, is the day the ancient Maya calendar ended.

There are constant references in the episode to Scully being assigned to the X-files "nine years ago," despite her being assigned to the X-files over ten years before, in March 1992.

SKINNER: Thirty government workers are ready to testify they witnessed Mulder push a military officer to his death.

DOGGETT: Killing the man who can't be killed?

[After Scully and Mulder enter the cave and meet the Cigarette Smoking Man, still alive]

CSM: What's the matter, Agent Mulder? You come to see the wise man, but you look as if you've seen a ghost.

MULDER: You're no wise man; you're a dead man, just like Krycek and X.

CSM: You see a dead man, Agent Scully?

SCULLY: I hoped and prayed you were dead, you chain-smoking son of a bitch.

CSM: You waste your time. Ask Mulder: He knows the futility of hopes and prayers. He knows the truth now.

[Final dialogue of the series]

SCULLY: You've always said that you want to believe. But, believe in what, Mulder? If this is the truth that you've been looking for, then what is left to believe in?

MULDER: I want to believe that the dead are not lost to us, that they speak to us as part of something greater than us - greater than any alien force. And, if you and I are powerless now, I want to believe that if we listen to what's speaking, it can give us the power to save ourselves.

SCULLY: Then we believe the same thing.

MULDER: (gets off the floor, crawls into bed with Scully, and whispers) Maybe there's hope.